Diurnal variation of phenylalanine concentrations in tyrosinaemia type 1: should we be concerned?

Abstract

Background: Tyrosinaemia type 1 (HT1) is treated with a tyrosine and phenylalanine-restricted diet, amino acids free of phenylalanine and tyrosine, and nitisinone (NTBC). Treatment guidelines recommend plasma tyrosine between 200-400 μm and phenylalanine at least >30 μm. There is little information on the diurnal variation of plasma tyrosine or phenylalanine in HT1. Low plasma phenylalanine <30 μm may be associated with poor growth and cognitive delay. The present study aimed to document diurnal variation of tyrosine and phenylalanine plasma concentrations and growth in children with HT1.

Methods: Median tyrosine and phenylalanine plasma concentrations were reviewed retrospectively over 3 years in 11 subjects (median age 4 years) with HT1. Subjects routinely collected morning fasting blood samples but afternoon nonfasted samples were taken in the clinic (<10% of samples). Growth Z-scores were calculated.

Results: The percentage of all plasma phenylalanine concentrations <30 μm was 8.6% and <40 μm was 13.6%. Only 2% of fasting morning phenylalanine concentrations were <30 μm, compared to 83% of nonfasting afternoon samples. All but one child had a height Z-score <0.

Conclusions: Blood phenylalanine concentrations were consistently lower in the afternoon. Taking blood samples at variable time points in the day may lead to variation in interpreting dietary control. A detailed study is necessary to examine the 24-h diurnal variation of plasma phenylalanine and tyrosine in HT1. It is possible that phenylalanine concentrations may be very low for a substantive time over 24 h and the potential impact that this may have on cognitive development and growth in children is unknown.